Glycyrrhetinic acid is the hydrolyzed product of glycyrrhizin (glycyrrhizic acid) which is an extract component of Glycyrrhizae Radix, possesses an antiphlogistic activity and an antipruritic activity, frequently used as therapeutic agents for eczema, dermatitis neurotica, and pruritus cutanea.
Glycyrrhetinic acid itself is easily soluble in pyridine and somewhat soluble in ethanol and chloroform but is almost insoluble in fats and oils, hydrocarbons, and water, which makes the preparation thereof difficult.
Now, in the treatment for pruritus cutanea such as a skin disease and insect bite, it is necessary to select a form of preparation suitable to treat the cause of the itching, various skin symptoms, etc. However, in solution, the solvent is evaporated off by the body heat to deposit crystals, whereby the sufficient medical effect cannot be obtained and also a sufficient durability of the medical effect cannot be expected. On the other hand, in ointments, etc., the deposition of crystals of medicament is unavoidable in the case that the medical component has poor compatibility with the base, and hence the medical effect and the duration of effect thereof cannot be obtained. An ointment causes a defect that the ointment stains clothes by the stickiness of the ointment itself. A plaster may be considered as the form of preparation having no such defects but such a product has not yet been known as to antipruritic agents.
Hitherto, it is known that glycyrrhetinic acid is soluble in crotamiton and fatty acid dialkylamides, such as capric acid N,N-dimethylamide, etc., (Japanese Patent Publication Nos. 25,405/'67 and 25,406/'67) but as the preparations of glycyrrhetinic acid, only a solution of glycyrrhetinic acid dissolved in a volatile solvent such as ethanol, etc., as a solubilizer, an ointment mainly composed of the acid and polyethylene glycol, and a hydrophilic ointment mainly composed of the acid and a carboxyvinyl polymer are known at present (see, for example, Japanese Patent Publication Nos. 25,405/'67 and 25,406/'67; Japanese Patent Publication (OPI) No. 47,520/'74, the term "OPI" indicates an unexamined published patent application open to public inspection).
Also, various forms of preparations are known containing glycyrrhetinic acid esters or the salts thereof having an improved water solubility or oil solubility, (Japanese Patent Publication (OPI) Nos. 149,222/'82 and 27,815/'84) but the form of plaster has not yet been known.
On the other hand, in the field of plasters, a percutaneous administration of various medicaments, in particular, steroid hormones, nonsteroidal antiflammatory agents, antibacterials, antitumor agents, etc., has hitherto been attempted. For example, U.S. Pat. No. 4,307,717 and European Patent No. 72,251 describe antipruritic agents such as benzoin, calamine, camphor, menthol, phenol, sulfur, etc., in the descriptions on various medicaments and suggest that these antipruritic agents can be used in the form of a flexible liquidabsorbent or an adhesive bandage for antipruritic purpose but the techniques disclosed therein cannot be applied to water-insoluble glycyrrhetinic acid.
Also, Japanese Patent Publication (OPI) Nos. 15,861/'83; 105,915/'83 and 36,608/'84 describe that glyctrrhetinic acid and materials similar to glycyrrhetinic acid can be widely used as medicaments with specific bases for medicines for external application but there are no descriptions of practical preparations and the techniques described in them cannot be applied as they are to glycyrrhetinic acid which is insoluble in water and scarecely soluble in fats and oils.
At present, plasters containing glycyrrhenitic acids for antipruritics use are not known.